The relevance of transposable element dynamics for host parasite interactions

转座元件(TES)是一种可移动的遗传元件，在真核基因组中占有很大比例。TE调控对维持基因组稳定很重要，部分是由小RNA执行的。我们最近发现了TE活性与寄生虫直接相关的证据，因为：(I)寄生虫转座酶(参与DNA TES插入基因组的酶)的表达在感染期间增加；(Ii)特定的小干扰RNAs(SiRNAs)调节寄生虫感染期间TES的活性。了解寄生虫的遗传基础和后果为改进寄生虫的治疗和控制提供了机会。本项目旨在研究TES在寄生线虫及其寄主环境中的作用。类圆线虫的生命周期有两个遗传上相同的阶段：一个是寄生的，感染人类和其他动物的肠道，一个是自由生活，不会造成伤害。我们将在自由生活的“控制”阶段和寄生阶段进行直接比较，以了解寄生过程中TE活动的变化以及TES是如何受到调控的。这个项目的结果将有助于我们在重要的和新兴的TE生物学和寄生虫学领域的知识。该项目解决了三个关键问题：1.寄生虫转座酶活性增加是否与宿主免疫反应有关？RNAseq将被用来识别不同宿主条件下寄生虫TE表达的变化，例如缺乏Th2(抗炎、抗线虫)或Th1(炎症)免疫反应，以建立寄生虫对宿主环境的TE反应。2.寄生虫感染过程中TE-sRNA活性是如何变化的？我们将量化TE在整个感染过程中的表达水平，并监测TE和调节它们的siRNAs是否在感染的早期、高峰和晚期有差异表达。我们将使用RNAi来靶向siRNA途径中涉及的基因，以表征TE调节途径。3.宿主TE活性在感染过程中是否发生变化？我们将在宿主(大鼠)组织上进行RNAseq，例如感染期间和感染后的肠道组织，以确定TE活性是否参与宿主对寄生虫的反应。申请者必须拥有学士学位或硕士学位，并对实验室和生物信息学工作感兴趣。成功的申请者将在亨特实验室(巴斯)工作，并将与海沃德(埃克塞特，佩林校区)、普罗塔西奥(剑桥)和赫斯特(巴斯)实验室的合作主管密切合作。学生将接受寄生虫学和RNA生物学方面的实验室技术培训，以及包括转录学和TE注释在内的生物信息学技能。

Transposable elements (TEs) are mobile genetic elements that comprise a large proportion of eukaryotic genomes. TE regulation is important for maintaining genomic stability and is in part carried out by small RNAs. We recently found evidence that TE activity is directly linked to parasitism because: (i) Expression of parasite transposases (enzyme involved in insertion of DNA TEs into the genome) increases during infection; (ii) Specific small-interfering RNAs (siRNAs) regulate the activity of TEs in the parasite during infection. Understanding the genetic basis and consequences of parasitism offers opportunities for improved treatment and control of parasites. This project aims to investigate the role of TEs in parasitism in the parasitic nematode Strongyloides and its host environment. The Strongyloides lifecycle has two genetically identical stages: one is parasitic and infects the intestine of humans and other animals, one is free-living causing no harm. We will make direct comparisons between the free-living 'control' and parasitic stages to understand how TE activity changes during parasitism and how TEs are regulated. The results from this project will contribute to our knowledge in the important and emerging field of TE biology and parasitism. The project addresses three key questions: 1. Is increased parasite transposase activity related to the host immune responses? RNAseq will be used to identify TE expression changes in the parasite under different host conditions e.g. absence of either a Th2 (anti-inflammatory, anti-nematode) or Th1 (inflammatory) immune response, to establish parasite TE responses to the host environment. 2. How does TE-sRNA activity in the parasite change during infection? We will quantify TE expression levels throughout infection and monitor if TEs, and the siRNAs that regulate them, are differentially expressed at early, peak and late stages of infection. We will use RNAi to target genes involved in siRNA pathways to characterise TE regulation pathways. 3. Does host TE activity change during infection? We will perform RNAseq on host (rat) tissues e.g. intestine, during and post-infection, to ascertain if TE activity is involved in the host response to parasitism. Applicants should have a strong first degree or masters with an interest in laboratory-based and bioinformatic work. The successful applicant will be based in the Hunt lab (Bath) and will work closely with co-supervisors in the Hayward (Exeter, Penryn Campus), Protasio (Cambridge) and Hurst (Bath) labs. The student will receive training in laboratory-based techniques in parasitology and RNA biology, and bioinformatics skills including transcriptomics and TE annotation.